Managing Cancer Risks

Here you will find information on BRCA cancer risks, cancer screening, surgical and medical options to decrease cancer risks in BRCA mutation carriers and information on the reproductive effects of BRCA. For information on BRCA testing, visit Genetic Risk Evaluation. If you are looking for information on cancer treatment, visit Cancer Treatment.

BRCA Cancer Risks

A positive BRCA1 or BRCA2 result means that a person has an inherited mutation in either gene and is at increased risk for certain cancers. The cancer risks associated with BRCA1 and BRCA2 in men and women carrying mutations are presented as ranges (see Table 1).

Table 1: Cancer Risk Ranges for BRCA1 and BRCA2 carriers

Lifetime BRCA1 and BRCA2 Cancer Risks for Women

Women with BRCA1 Mutation

Women with BRCA2 mutation

Average woman in US without mutation

Type of Cancer

Breast

60-80%

50-70%

13%

Ovarian

30-45%

10-20%

1-2%

Pancreatic

2-3%

3-5%

1%

Melanoma

-

3-5%

1-2%

Lifetime BRCA1 and BRCA2 Cancer Risks for Men

Men with BRCA1 Mutation

Men with BRCA2
mutation

Average man in US without mutation

Type of Cancer

Breast

1-5%

5-10%

0.1%

Prostate

*

15-25%*

16%

Pancreatic

2-3%

3-5%

1%

Melanoma

-

3-5%

1-2%

* Although there is no convincing evidence of overall increased risk of prostate cancer, men with BRCA1 mutations may develop prostate cancer at a younger age than men in the general population. BRCA2 mutations are associated with an increased risk of prostate cancer, which also can be of earlier onset.

The cancer risks associated with BRCA1 and BRCA2 in men and women carrying mutations are presented as ranges (see Table 1), since cancer risk may vary in different families or population groups.

As more individuals undergo genetic testing and more studies to assess risk are published, our understanding of cancer risk in individuals with BRCA1 and BRCA2 mutations continues to evolve. For these reasons, risk estimates may vary from one source to the next and as research advances.

At present, we cannot predict where in the risk range any individual will fall. There are other genetic and lifestyle factors that can influence, or modify cancer risk associated with mutations in BRCA1 and BRCA2. Discovering these factors and refining our understanding of the risk associated with them may help us provide a more accurate individual risk assessment. The Basser Center is actively working on studies to uncover the factors that may help individualize risk assessment.

In addition to the cancers specifically listed in Table 1, men and women with BRCA mutations appear to have a slightly increased risk of developing cancers in general. Therefore, regular medical follow-up with prompt attention to symptoms is strongly encouraged. For example, symptoms of unexplained weight loss, unexplained and persistent pain, swollen lymph nodes, and sores that do not heal should be evaluated by a physician.

Managing Cancer Risks in Carriers: Overview Screening

A cancer risk management plan is typically tailored to a persons unique circumstances and preferences.

A personalized cancer risk management program can be developed for individuals known to be at increased cancer risk due to a mutation in BRCA1 or BRCA2. You and your doctors will ultimately decide what plan makes the most sense for you.

Cancer risk management generally includes the following categories:

Intensive screening to optimize the chances of early detection, should cancer develop.

Prophylactic or risk reducing surgical removal of ovaries and consideration of prophylactic removal of the breasts.

Chemoprevention, which is taking a medicine shown to lower the chances of developing cancer.

Screening guidelines are detailed in table 2, with the basics described below.

Breast Cancer Screening: In general, it is recommended that women with BRCA1 or BRCA2 mutations get more intensive breast screening, starting at an earlier age (age 25), discussed below. Men with BRCA mutations also require evaluation for elevated breast cancer risk, as detailed below.

Ovarian Cancer Screening: Ovarian cancer screening has major limitations but should be considered as detailed below.

Melanoma Evaluation: In general, it is recommended that women and men with BRCA1 or BRCA2 mutations be especially diligent about getting new moles or moles that have changed evaluated, as detailed below.

Pancreatic Cancer Screening: Men and women with mutations, primarily in BRCA2, may consider pancreatic cancer screening, especially if there is family history of the disease, as discussed below.

Prostate Cancer Screening: It is recommended that men with BRCA mutations start prostate cancer screening starting earlier, at age 40, as detailed below.

General cancer screening recommendations such as colonoscopy beginning at age 50 and pelvic exam with pap smear beginning at age 18 should also be followed by carriers, in addition to the more intensive cancer surveillance recommended for BRCA-related cancers discussed above.

Family history of cancers should always be shared with your doctor when determining specific screening recommendations. For example, if there is an early onset colon cancer in your family, you may need to have your first colonoscopy at a younger age.

For more information on general population screening recommendations to discuss with your doctor, visit the American Cancer Society.

Managing Cancer Risks in Carriers: Screening Detailed

The following screening procedures are recommended for women and men found to have a mutation in either BRCA1 or BRCA2 (listed in Table 2).

Generally, cancer that is detected in earlier stages is more easily treated, and outcomes are often more favorable.

Individuals with BRCA mutations should also diligently follow all additional cancer screening recommendations for individuals at average risk. For example, screening recommendations for cervical and colon cancers should be carefully followed. For more information on general population screening recommendations to discuss with your doctor, visit the American Cancer Society.

In addition, any moles which are new or changing should be evaluated by a doctor.

Note that screening recommendations for BRCA1/2 carriers may change as research evolves and we develop better methods for detecting cancer early.

The following screening procedures are recommended for women and men found to have a mutation in either BRCA1 or BRCA2 (listed in Table 2).

Table 2

Screening for Women with Mutations in BRCA1 or BRCA2

Type of Cancer

Screening Procedure

Starting Age

Frequency

Breast

Breast Self Exam

18 years

Once every month

Physician Breast Exams

25 years

Every 6-12 months

Breast MRI2

25 years1

Every 12 months

Mammograms

30 years1

Every 12 months

Ovarian

CA-125 blood test
Ovarian ultrasound
Note: These tests have never proven to reduce the risk of dying from ovarian cancer

Age 30 or 5-10 years prior to earliest onset, until childbearing complete, then removal of ovaries (prophylactic oophorectomy), ideally between age 35-40

Every 6-12 months

1. Annual breast mammography may be recommended between age 25-29 if breast MRI is unavailable. Age to begin breast MRI and mammography is individualized based on earliest age of onset of breast cancer in the family.

2. If MRIS's are obtained from other facilities, it is important to use an MRI set up specifically for breast imaging.

Screening for Men with Mutations in BRCA1 or BRCA2

Screening Procedure

Starting Age

Frequency

Type of Cancer

Breast3

Physician Breast Exams

35 years

Every 6-12 months

Prostate

Prostate Exam and PSA blood test

40 years

Once every year

3. Consider baseline mammogram at age 40 and annual mammogram if significant breast tissue is present or if indicated by baseline mammogram.

Breast cancer screening aims to detect breast cancer early when it is most treatable. Screening for breast cancer will not decrease the chance that cancer will develop. However, intensive screening for breast cancer helps to detect breast cancer early when it is most treatable.

Over the years, researchers have developed specialized breast cancer screening strategies for BRCA1/2 carriers. This approach involves starting screening at an earlier age and using several different methods at regular intervals.

Intensive breast cancer screening or surveillance starts at age 25 for BRCA-positive women, though it may be recommended that an individual start screening earlier based on the earliest breast cancer in the family. Clinical breast exam is recommended every 6-12 months starting at age 25. Between ages 25 and 29, it is recommended that annual breast MRI (or mammogram if breast MRI is unavailable) be performed. Between age 30 and 75, annual breast MRI AND mammography is recommended. Sometimes, the imaging studies- mammogram and breast MRI- are staggered so that a breast MRI is followed by a mammogram 6 months later. For women older than 75, breast cancer surveillance should be managed on an individual basis.

It is recommended that women who carry BRCA mutations have "breast awareness" which includes breast self exam, beginning at age 18. Given that many women will not undergo genetic testing until 25, breast self exam can be considered by all women from families with BRCA1/2 mutations. Breast awareness means a woman is familiar with her breasts and promptly reports changes to their health care provider.

Starting at age 35, male BRCA carriers should begin self breast exams and undergo chest wall exams every 6-12 months with a physician. At age 40, a baseline mammogram may be considered. Depending on the results and amount of breast tissue, annual mammograms may be recommended.

A mammogram is a low-dose X-ray procedure that produces images of the inside of the breasts. Mammography can detect some suspicious breast changes that are too small or too deep to be felt on breast examination.

A breast MRI (Magnetic Resonance Imaging) uses magnets and radio waves to create clear detailed pictures of the inside of your breasts. The breast is in mild compression during the procedure and you are lying on your stomach. Frequently, an intravenous injection is necessary for the best imaging.

Deciding on a cancer screening regimen involves weighing the benefit of diagnosing a cancer early against the risks of the screening test.

Mammograms use radiation to image the breasts and radiation exposure can theoretically increase cancer risk. Therefore, the benefit of detecting a breast cancer early with a mammogram must outweigh the small risk that the radiation could cause harm in order for a mammogram to be recommended.

Some studies indicate that for BRCA1/2 carriers under age 30, the risks of mammography are greater than the benefits. This is in part because there are few breast cancers in BRCA1/2 carriers under 30, with breast cancer risk before age 30 ranging from 1-2% (see graphs 1 and 2). Guidelines for managing BRCA positive women recommend that between the ages of 25-29, annual breast MRI—or mammogram if breast MRI is not available—be performed. Starting at age 30, annual breast mammography is recommended in conjunction with annual breast MRI and clinical breast exam every 6-12 months.

Screening regimens are individualized based on family history and should always be discussed with your doctor.

The available methods for ovarian cancer screening often fail to detect ovarian cancer at an early stage. It is therefore recommended as an interim measure for women who have not yet elected risk-reducing oophorectomy as discussed below.

Ovarian cancer screening involves a transvaginal ultrasound and a blood test called CA-125 every 6-12 months starting at age 30 or 5-10 years before the earliest ovarian cancer in the family.

Ultrasound is an imaging technique that uses sound waves that bounce off of tissues and provide a picture of whatever is being investigated. By inserting an ultrasound probe into a woman's vagina, doctors can get a relatively good look at her ovaries. However, transvaginal ultrasound often fails to detect ovarian cancer at an early stage and can detect changes in the ovaries that are not actually cancer.

CA-125 is a protein in the blood that is shed from damaged ovary cells and is often elevated in ovarian cancer. However, CA-125 can also be elevated for other reasons unrelated to cancer. Also, many early stage ovarian cancers do not cause an elevated CA-125.

There are multiple research studies currently being conducted through the Basser Research Center for BRCA that aim to find better methods for detecting BRCA-related cancers early. It is hoped that these studies will find even better ways to manage high-risk individuals. Current cancer screening opportunities for which you are eligible can be discussed with your local BRCA specialist. Pancreatic cancer screening is not yet proven but is frequently offered to BRCA carriers, especially those who have a history of pancreatic cancer.

Managing Cancer Risks in Carriers: Oophorectomy & Mastectomy

Prophylactic mastectomy is the surgical removal of one or both breasts. It is the most aggressive and effective preventive strategy available to reduce breast cancer risk.

Some women with BRCA mutations choose this option. Studies have shown that this procedure lowers breast cancer risk by at least 90 percent in women with BRCA1 and BRCA2 mutations. Therefore, breast cancer risk is significantly lowered bythis procedure.

However, as screening for breast cancer is usually effective in finding breast cancer at an early stage, particularly when MRI is used as one of the screening components, screening is a valid alternative to prophylactic mastectomy.

It is worth noting that even early stage breast cancers may require chemotherapy; this can impact some women's decisions. Intensive screening can also be used in combination with preventive medications.

Reviewing one's breast cancer risk by age or decade with a genetic counselor can be helpful in determining if and when to consider and fully explore the option of prophylactic surgery.

Surgery is a very personal decision and we recommend women fully investigate all their options. For women considering this prophylactic mastectomy, it is often helpful to consult with a plastic surgeon to learn about options for breast reconstruction.

We encourage all women who would consider this option to take the time they need to make a thoughtful decision.

In determining when to start breast cancer screening and in considering risk reducing surgery, understanding how breast cancer risks evolves over the course of lifetime can be helpful. The below graphs of breast cancer risk by age are from a meta-analysis, which is a study that combines results from many studies to gain the best estimate of risks. They show the risk of breast cancer developing by different ages.

You may note that the average breast cancer risk to age 70 in these graphs is on the lower end of the range for lifetime cancer risks in carriers cited earlier. The lifetime risk numbers on this website are still correct; they simply reflect different studies done in carriers of BRCA1 and BRCA2. Furthermore, these graphs only capture risk to age 70 and other studies have captured risk to later ages.

The graphs of risk by decade are most helpful for understanding the trends in cancer risk in the course of a lifetime, rather than exact risks at a given age.

It is strongly recommended that women who carry BRCA mutations remove their ovaries (oophorectomy) and fallopian tubes after childbearing has been completed. The major decision is related to the timing of the procedure.

Current guidelines recommend oophorectomy by age 35-40. Recent studies suggest that this approach will reduce ovarian cancer incidence by as much as 70- 90 percent.

However, some women will still develop cancer of the lining of the abdomen, a disease that behaves like advanced ovarian cancer.

In addition to markedly reducing ovarian cancer risk, it appears that removing the ovaries from pre-menopausal women also reduces breast cancer risk by 50-60 percent. Therefore, the overall benefit of this surgery is very significant.

This is important since screening for ovarian cancer is very limited and usually does not detect ovarian cancer in the early stages. Fallopian tube cancers are very rare, but occur more frequently in women with BRCA1 and BRCA2 mutations. It is routine that fallopian tubes be removed at the time of oophorectomy.

The risk of ovarian cancer (and the average age of developing ovarian cancer) do differ between BRCA1 and BRCA2 mutation carriers. Therefore, it is important to discuss with your providers these issues and how they relate to the timing of the procedure.

Removing healthy ovaries in a post-menopausal woman is not expected to have an impact on her symptoms of menopause. Once a woman is post-menopausal, and has not had a period for at least a year, her ovaries no longer function to produce estrogen.

The risk of ovarian cancer (and the average age of developing ovarian cancer) does differ between BRCA1 and BRCA2 mutation carriers. Therefore, it is important to discuss with your providers these issues and how they relate to the timing of the procedure. The below graphs provide information on ovarian cancer risk by age for carriers of BRCA1 and BRCA2. Current guidelines recommend oophorectomy by age 35-40.

You may note that the average ovarian cancer risk to age 70 in these graphs is on the lower end of the range for lifetime cancer risks in carriers cited earlier. The lifetime risk numbers on this website are still correct; they simply reflect different studies done in carriers of BRCA1 and BRCA2. Furthermore, these graphs only capture risk to age 70 and other studies have captured risk to later ages.

The graphs of risk by decade are most helpful for understanding the trends in cancer risk in the course of a lifetime, rather than exact risks at a given age.

Removing the ovaries in a pre-menopausal woman will cause her to enter menopause, since the ovaries provide a woman with her major source of estrogen. Because of this, prophylactic oophorectomy is
only considered after a woman is sure she has completed her family.

In addition, ovarian cancer risk becomes more significant for women in their 40s, 50s, and beyond. Even in women with BRCA mutations, it is uncommon to be diagnosed with ovarian cancer before the age of 40.

Some women choose to have their uterus removed at the same time their ovaries are removed. There are both advantages and disadvantages to this approach. Removal of the uterus is called a hysterectomy.

Tamoxifen (see below under What is chemoprevention?) is a medication that some BRCA carriers elect to take in order to reduce their risk of breast cancer. It is associated with a slightly increased risk for uterine cancer.

A second issue related to hysterectomy is that the type of hormone replacement therapy for premenopausal women who have their ovaries removed depends on whether a woman still has her uterus (see below). Hormone replacement therapy can be simplified if no uterus is present (see below).

Finally, there is a theoretical risk of developing cancer where the fallopian tube was connected to the uterus. These are reasons some women consider hysterectomy.

However, the recovery time for surgery involving the removal of both the uterus and the ovaries is longer than for surgery to remove only the ovaries. The only "required" surgery is the removal of the ovaries and fallopian tubes. You should discuss these issues in greater detail with your physicians.

While prophylactic oophorectomy reduces ovarian and breast cancer risk, there are additional health issues that need consideration. Estrogen provides women with major protection from bone loss (osteoporosis), a condition where the bones are weakened and more easily fractured. In addition, estrogen deprivation at a young age increases a womans risk of heart disease.

Pre-menopausal women who undergo prophylactic oophorectomy may also experience some uncomfortable effects of menopause, such as hot flashes, vaginal dryness, mood swings and sleep disturbances.

The limited available data suggest that short-term hormone replacement therapy (HRT) does not increase breast cancer risk in BRCA mutation carriers. Therefore, women with BRCA mutations and no history of breast cancer typically have the option of hormone replacement therapy for several years after having their ovaries removed. Hormone replacement therapy is usually stopped between ages 45-50.
This is because the hormone replacement dose is lower than the dose of estrogen that would be produced by the ovaries if not removed.

Thus even with HRT, removal of the ovaries results in a significant decrease in estrogen exposure. The benefits of taking estrogen may include prevention of osteoporosis, as well as control of post-menopausal symptoms such as vaginal dryness, hot flashes and sleep disturbances.

Multiple studies have demonstrated a small increase in the risk for breast cancer in women who use combination (estrogen plus progesterone) post-menopausal HRT for more than five years. For this reason, post-menopausal women, over the age of 50 with mutations in a BRCA gene should consider alternatives to traditional HRT.

These alternatives, including tamoxifen and raloxifene (discussed further below), will not help symptoms of menopause such as hot flashes (and may make them worse). Other medications are available to decrease these symptoms.

While there are no long-term studies to support or discourage use of HRT by post-menopausal women with mutations in a BRCA gene, this is the most cautious approach at present.

Women with a previous breast cancer diagnosis are also discouraged from using HRT.

Your physician can discuss the pros and cons of hormone replacement therapy with you in detail.

In general, data suggests that women who undergo natural menopause and take combination estrogen and progesterone hormone replacement therapy, have a slight increased risk of heart disease, stroke and breast cancer. There is some evidence to suggest that breast cancer and heart disease risk may be worsened by the addition of progesterone to estrogen.

Progesterone needs to be taken with estrogen only in women who still have a uterus, while women without a uterus can take estrogen alone. More recent work suggests that hormone replacement therapy consisting of estrogen only does not affect breast cancer risk and may decrease cardiovascular events.

We recognize that many women at high risk of breast cancer will feel anxious about taking hormonal medications. Discussions with your doctors are usually helpful in making these difficult decisions.

These alternatives, including tamoxifen and raloxifene (discussed further below), will not help symptoms of menopause such as hot flashes (and may make them worse). Other medications are available to decrease these symptoms.

While there are no long-term studies to support or discourage use of HRT by post-menopausal women with mutations in a BRCA gene, this is the most cautious approach at present.

Women with a previous breast cancer diagnosis are also discouraged from using HRT.

Chemoprevention & Oral Contraceptives

Chemoprevention, taking a medicine in an attempt to lower cancer risk, can provide additional choices for high-risk women. There are several medications available; tamoxifen, raloxifene, and aromatase inhibitors are discussed below.

There is very limited, if any, data on these medications specifically in BRCA1 and BRCA2 mutation carriers.

Tamoxifen is a selective estrogen receptor modulator (SERM) that has been used for more than 30 years to treat women with breast cancer. Usage is also associated with reduced numbers of breast cancer occurrences in the opposite breast.

A national study of over 13,000 healthy women at increased risk determined that tamoxifen can lower the risk of developing breast cancer by 49 percent. This finding was very significant, and tamoxifen is the first FDA approved medication shown to lower breast cancer risk in healthy women.

Tamoxifen was also associated with some protection from bone loss in postmenopausal women.

Drawbacks to taking tamoxifen include a small risk for early stage uterine cancer and a small increase in the risk for pulmonary embolism (a blood clot in the lung), deep vein thrombosis (a blood clot in a major vein), and cataracts.

Raloxifene (also called Evista) is also a selective estrogen receptor modulator (SERM) shown to have positive effects on bone density and cholesterol levels. However, raloxifene has been shown to block the actions of estrogen on both the breasts and uterus and therefore, is not associated with an increase in risk for uterine cancer.

Raloxifene is effective in preserving bone density in post-menopausal women and is currently being used for this purpose. Raloxifene may also have positive effects on the risk for heart disease. While raloxifene lowers the levels of LDL (the "bad" cholesterol) and increases the level of HDL (the "good" cholesterol), these effects have not yet been shown to be protective from heart disease. Raloxifene has also been shown to decrease breast cancer risk.

The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene is nearly as good as tamoxifen in reducing the risk of invasive breast cancer in postmenopausal women.

Raloxifene is associated with lower risks of blood clots and endometrial cancer. Raloxifene may be associated with a slight increase in the risk of blood clots, including pulmonary emboli (a small blood clot in the lung) in older women, so the risks versus benefits of this medicine should be carefully considered.

Like tamoxifen, raloxifene has risks that must be weighed against the benefits in consultation with your physician. Raloxifene can be an excellent choice for women at increased risk for breast cancer with bone density loss, since this medicine provides the dual benefit of building bone mass while lowering breast cancer risk.

Aromatase inhibitors (AI's) are another class of medications being investigated for their ability to prevent breast cancer. AI's are currently used to treat post-menopausal estrogen and progesterone receptor positive breast cancers.

In post-menopausal women, a main source of estrogen comes not from the ovaries, but from the break-down of fats and other hormones into estrogen. AI's stop this conversion and reduce the amount of estrogen in the body. They reduce the risk of recurrence of breast cancer and an initial study has shown that once of the AI can reduce the development of breast cancer.

There have been several studies published examining the safety of birth control pills in women who have BRCA mutations. Oral contraceptives work in part by preventing a woman from ovulating. Anything that prevents a woman from ovulating is usually associated with a decreased risk for ovarian cancer.

Some studies suggest that the risk reduction for ovarian cancer can be as much as 50%.

However, there are some conflicting findings about the association between birth control pills and breast cancer risk. Some studies have shown there may be a small increased risk of breast cancer associated with these medications. However, many of these studies included women who were on higher dosages of hormones prior to the 1970's. Current formulations of birth control pills have lower hormone levels, and may therefore be associated with lower risks.

More research is underway to help answer these important questions. Ultimately, balancing the risk of breast cancer (for which we do have effective screening), against the significantly reduced risk for ovarian cancer, and the potential need for effective birth control is complex. Discussion of the benefits and risks on an individual basis is strongly encouraged.

Many BRCA carriers accept the 50% risk of passing on a BRCA mutation to their children. Whether to use reproductive technologies to avoid passing on genetic diseases is a very personal decision that many individuals and couples face.

For those who want to consider using these technologies, Preimplantation Genetic Diagnosis (PGD) is a special form of in vitro fertilization (IVF). This can be an option for individuals who carry a known genetic condition and wish to eliminate the chances of passing it on to a child. PGD is also known as "embryo screening" and is performed in a laboratory.

This procedure is used in combination with IVF to test embryos (fertilized eggs) for a specific genetic mutation, such as a BRCA1 or BRCA2 gene mutation. The testing is performed before transferring the embryo into the woman's womb. The embryos that test negative for the known mutation will be transferred into the woman. The genetic mutation must first be identified in the parent, whether male or female, in order to perform PGD. PGD is a procedure that helps prevent having a child with the same gene mutation identified in a parent; however, PGD does not guarantee that the transferred embryos will lead to a full-term, healthy pregnancy.

PGD is costly and while insurance may cover a portion of the cost, insurance may not cover the procedure at all. While PGD is expensive, costs seem to be decreasing with time. Talk to a fertility specialist or IVF clinic to gain more information on PGD.